Synthesis of Thiolated Chitosan as Matrix for the Preparation of Metformin Hydrochloride Microparticles

Abstract

Thiolated chitosan is synthesized by reacting chitosan and cysteine as the carriers of thiol groups with 1-ethyl-3-(3-dimethylamino propyl) carbodiimide (EDAC) as catalyst. The properties of thiolated chitosan was then characterized, and being formulated with metformin HCl and sodium tripolyphosphate (STPP) to form microparticles. Metformin HCl microparticles tested for drug release use type II dissolution tester (paddle). Statistical data analysis performed using one-way ANOVA test followed by t-test significance level of at least P <0.05. The results showed that thiolated chitosan formed a slightly yellowish white solid, distinctive smells, looks fibrous, soluble in acid, in water, and mixed with water to form transparent gels with high viscosity. Chitosan-cysteine conjugates synthesized by the addition of 50 mM EDAC has the highest content of thiol groups of 265,169 µmol per 50 mg of conjugates. Mucoadhesive test in vitro using rotating cylinder showed that thiolated chitosan with the addition of 50 mM EDAC was able to adhere to the fresh cow's intestine for more than 10 hours. Release profiles of Metformin HCl microparticles showed that the chitosan-cysteine conjugates can be used as a matrix for the controlled release dosage forms. The lowest rate of drug release was found in microparticles using thiolated chitosan with the addition of 50 mM EDAC, seen at minute 360, a drug that released of 26,256%. The release of metformin HCl from microparticles are more likely to follow the kinetics of drug release according to Higuchi equation.